'Acting was my way of getting noticed' ... Alex Kingston in her dressing room. Photograph: Graham Turner for the Guardian

The moment Alex Kingston really started to worry about playing Lady Macbeth – and all the unwelcome spirits the play is said to stir up – was when her 12-year-old daughter, Salome, began sleepwalking. In the days before Kingston left her home in Los Angeles for rehearsals in the UK, Salome asked to share her bed – and every time she got stuck into the script, her daughter's sleep was disturbed. "If I was doing something else, or my mind was somewhere else, she would sleep," says Kingston. "But if I started thinking about the text, or working on it, she would start sleepwalking. It began to freak me out."

To quell her nerves, Kingston bought crystals, and is now sleeping with them beneath her pillow. "Just as a psychological pacifier," she says. "Anything would have done – it could have been a teddy."

Actors have been talking about the curse of Macbeth since its first days on the stage in the early 17th century, when the boy who played the notorious sleepwalker Lady Macbeth was rumoured to have died of a fever. Since then, it has been held responsible for countless deaths, storms, fires and falling scenery. "I know this will probably sound very, very new-agey," says Kingston, with the glint of camp she often brings to roles, "but I think I'm also going to say some sort of prayer at the end of each performance, just to try and shut it down."

There are two distinct sides to Kingston the actor. She has lived in LA ever since she was cast in ER at the end of the 1990s, and definitely has a Hollywood edge, buying crystals and talking about her "life journey". But she is also from a generation of British women specialising in strong characters, steeped in the classics, with perfect vowels and a hint of hockeysticks. Over the years, Kingston, who joined the Royal Shakespeare Company early in her career, has moved from one swashbuckling role to another: Moll Flanders, Boudica, River Song in Doctor Who. She is, however, much more self-aware and straightforwardly funny than either of these sides suggests, coming across as the sort of person who would never knowingly be rude to a waiter, always on the verge of telling a good joke about herself.

Now she's about to play the character often seen as the pinnacle for female actors, opposite Kenneth Branagh, who is co-directing the play with Rob Ashford. For those lucky enough to get tickets, it's a chance to see the actors up close: the play is being performed in a deconsecrated church next month, as part of the Manchester international festival. The final performance will be shown in UK cinemas, through the National Theatre Live programme.

Macbeth has sometimes been described as Shakespeare's most misogynist play, on the basis that, arguably, so much of its malevolence originates from the female characters, not least the witches. But that's not how Kingston sees it. She has obviously considered the argument that Lady Macbeth, who entreats her husband to kill the king and seize power, is rotten to the core. "But if you just play that, it's only one or two notes. Whereas I think it's much more interesting to explore the question: what if these people were just your average husband and wife, and they were presented with this seemingly extraordinary opportunity – how far would they go? One reads that [story] in the rags every week. You know, people suddenly turning bad, doing something completely out of the ordinary, and the public not knowing why it happened."

Over the past five years, Kingston has reached a new audience with Doctor Who, and reacts with playful, cagey laughter when asked if she'd like a woman Doctor to replace the outgoing Matt Smith. "Spoilers!" she laughs, repeating one of her character's buzzwords. "I can't say." Given that River, a time-travelling archaeologist, has been romantically involved with the Doctor, such casting could be especially progressive, creating a gay relationship for the chief protagonist. "Well, you know, I wouldn't put it past Steven," she says, referring to the show's lead writer and executive producer, Steven Moffat. She agrees this would be brilliant. "Certainly, River has always talked about 'the special one' when referring to the Doctor."

Playing a time-traveller must have been especially pleasing in an industry obsessed with age. Now 50, Kingston says it is becoming harder to find work in the US. "When it comes to pilot season, when thousands and thousands of pilots are cast, and only eight are suitable for you – it's a really awful statistic." The year before last, she tried for a pilot "and the response was: 'She hasn't had plastic surgery.'" No plastic surgery, no part.

In fact, that year she was turned down for every role she auditioned for: "Not young enough, not old enough, not slim enough, not plastic surgeried enough ... I know people say England is absolutely going down that same path as America, and there is more pressure on women here as well, but it's not nearly as bad. Largely, that's to do with the fact that we still have theatre. And also, I think, the public want to see people they can relate to, who still look like them."

Kingston grew up in Epsom, Surrey, with her father, who worked as a butcher, her mother and two younger sisters. Her middle sister, Susie, three years her junior, was born with physical and mental disabilities, so her mother "basically stopped any career and has been a caretaker at home". As a child, Kingston says she was lost in a fantasy world, and suspects her sister's condition may have had a bearing on her decision to become an actor. "Given the amount of work and time my mum devoted to my sister, it left me a lot of time to play on my own. I mean, I played with kids in the street all the time, too – I definitely wasn't denied a childhood. But I do wonder whether, in a sense, acting was my way of getting noticed."

She is "numerically dyslexic", she says, but managed to get into a girls' grammar school. While there, she attended a drama club and picked up roles in Grange Hill (as a judo-kicking bully) and a St Trinian's film (as a sexy sixth former). At Rada, she met and fell in love with Ralph Fiennes; when he joined the RSC, she was determined to follow him. "I just thought, 'I have to be part of that company, because our relationship will not last if I'm not.' So I worked hard and got in."

This sudden success left her wondering what to do next. Then her 12-year relationship with Fiennes foundered, they divorced, and she moved to Hollywood, cast as the clever, forthright surgeon Dr Elizabeth Corday in ER. During her run in the show, she married German journalist Florian Haertel and had Salome; the couple have since separated.

One of her odder experiences on ER came about due to an interracial relationship Dr Corday had with fellow surgeon Peter Benton, played by Eriq La Salle. This relationship was so unusual on US TV that, apparently in order to make sense of it, many viewers simply assumed Kingston was black. Prior to moving to the US, she had been living in Peckham, London, where "you see interracial relationships all over the place. I kind of naively thought it would be even more liberal in America. And it couldn't have been further from the truth. In fact, I'm trying to think if there's a television show right now where there's an African American and Caucasian relationship. They're few and far between."

Kingston is often characterised, and cast, as preternaturally strong, a warrior woman, but she says the truth is more mixed. "I'm actually very vulnerable and sensitive," she says, quickly following this remark with a high, mocking "Oh!" As well as her daughter's sleepwalking, Lady Macbeth has been a source of other worries, given that it has already been performed by everyone from Sarah Siddons, the great Welsh tragedienne of the 18th century, to Judi Dench. "This terror started to creep in, and I emailed Ken and said, 'I'm getting actually really rather nervous.' And he said, 'Don't think of it as nerves, think of it as excitement.' So I was like, well," she takes a deep breath, "I'm very, very, excited!"

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